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ARTICLE IN BRIEF

Neurologists in states where medical marijuana is legal discuss the requests they are getting from patients and how they are addressing them.

With more and more patients asking about medical marijuana treatment for their neurological conditions — or asking for the certification paperwork allowing them to use it — neurologists are struggling to navigate the confusing terrain.

But neurologists in states where medical marijuana is legal say that they have granted relatively few certifications for its use. Most associations have not made education about medical marijuana a high priority at meetings, and only now are they beginning to roll out such sessions in a limited way.

In an AAN evidence-based review of complementary and alternative medicine therapies for multiple sclerosis (MS), published March 25 in Neurology, the guideline authors reviewed studies on oral cannabis, medical marijuana pills, and oral medical marijuana spray, among other alternative therapies for MS. The evidence suggests these therapies may ease patients' reported symptoms of spasticity, pain related to spasticity, and frequent urination, the guideline authors wrote.

COLORADO: ‘GROUND ZERO’

In Colorado — legalized marijuana's ground zero, where use for medical purposes was made legal in 2000 and legal sales for recreational use began in January — consideration of the treatment has been growing, but slowly, said Scott London, MD, president of the Colorado Society of Clinical Neurologists.

“It's been a sticky issue,” he said. At first, doctors associated with marijuana dispensaries did nearly all the writing of certifications, he said. “We had to be careful about who we selected and not to over promote it, lest our reputations, in our minds, might be somehow tarnished — although in truth that really hasn't happened.”

“Lately, I think there's been more acceptance among neurologists for a few indications,” he added. Those conditions have been primarily chronic pain, epilepsy, migraines, and spasticity and pain associated with MS.

Dr. London said he has filled out paperwork for two patients with significant motor disabilities and spasticity from MS. In both cases, the patients requested it.

“It's been one more thing for their treatment,” Dr. London said. “I think one fellow has stayed on it and the other has not.” The patient who stopped using marijuana did so because it was ineffective, he explained.

Dr. London said several children of his elderly patients have asked about it for their parents, generally to help with pain; on subsequent appointments, he has learned that their parents tried medical marijuana from a dispensary.

“We've had a few interesting experiences where these patients just did not have any idea quite what they were getting into,” he said. “And they ended up very altered cognitively and not particularly interested in doing more medical marijuana.”

WHAT ABOUT CHILDREN?

Medical marijuana became legal in Massachusetts in 2012. But Phillip Pearl, MD, director of epilepsy at Boston Children's Hospital, said requests for marijuana treatment for seizure prevention have increased dramatically since Dr. Gupta's special, “Weed,” highlighted the case of Charlotte Figi, a 7-year-old girl with Dravet syndrome whose seizure count plummeted after twice-day treatment with a form of marijuana that is high in cannabidiol (CBD), a non-psychotropic compound, and low in tetrahydrocannabinol (THC), the psychoactive compound that brings on altered cognitive effects. The version has since been dubbed “Charlotte's Web” for use in children.

[When all other treatment options failed, Charlotte's parents, Paige and Matt Figi, found two physicians (non-neurologists), one in Colorado and one in Massachusetts, to sign for the medical marijuana certificate, and were able to get the compound mix from a dispensary in Colorado.]

Dr. Pearl said child neurologists are generally willing to try the therapy, but only in intractable cases. “I would say most child neurologists would be very sympathetic to a trial of cannabinoid in a patient with Dravet syndrome who is having active seizures or any child who is having very active mixed generalized seizures,” he said.

But he stressed that, for most cases of pediatric epilepsy, there are many established options, from medications to surgeries to diets.

“It's not as if there aren't any treatment options for most patients and it's not that common to see a child who doesn't have any promising treatment options left,” he said.

Orrin Devinsky, MD, FAAN, the director of the Comprehensive Epilepsy Center at New York University (NYU), said it's important to remember medicine's fundamentals. “We need to stay focused on the basic tenets of medicine,” he said. “Because marijuana is considered natural, some parents may favor this over an established therapy as the initial or early therapy. I don't support this because we do have medicines that have been fairly well studied. By contrast, for treatment-resistant cases, it is worth considering. But most importantly, we need more objective research data.”

There is a place to try medical marijuana in certain cases, he offered.

“For those patients with treatment-resistant epilepsy who have failed several medications, often many medications, and for whom available options are not promising, and [who] may have exhausted dietary therapies [and] vagus nerve surgical therapies, I think that medical marijuana is an extremely reasonable option at this time,” he said.

A CLINICAL TRIAL UNDERWAY

Along with investigators at the University of California–San Francisco's Benioff Children's Hospital, Dr. Devinsky at NYU is hoping to enroll 25 children with intractable forms of epilepsy, ages 1 to 18, in an open-label trial of a drug called Epidiolex, manufactured by UK's GW Pharmaceuticals. Epidiolex is a 98 percent CBD version of marijuana that comes in a liquid form and contains no THC. The Food and Drug Administration granted orphan drug designation of the drug for treating Dravet syndrome in November 2013; in February, the federal agency extended that designation to Lennox-Gastaut syndrome. The yearlong study will primarily assess safety and tolerability; pending FDA approval, the trial will expand to four additional institutions this year.

In April 2013, the drug was given to two patients who were part of a special exploratory study approved by the FDA's Investigational New Drug program, and results from that initial experience helped provide the framework for the current study, according to researchers at UCSF.

“Studies in animal models have shows CBD works as an anticonvulsant, but this is just the initial exploratory step to determine whether further testing of CBD as an anticonvulsant is warranted, and how it will be conducted,” said Maria Roberta Cilio, MD, PhD, principal investigator for the multicenter study and director of research at the UCSF Pediatric Epilepsy Center, in a statement on the university's website. “Our current trial will hopefully lead to a placebo-controlled, blinded clinical trial in the types of epilepsy that respond best to CBD.”

“Everyone needs to be humble — doctors, patients, families — that we don't have answers,” Dr. Devinsky told Neurology Today. “We don't know about the safety, we don't know about the efficacy for any epilepsy syndrome.”

PRESCRIBING FOR ADULTS

What about adult use? Eduardo Garcia, MD, president-elect of the Massachusetts Neurological Association, said the requests for adult use of medical marijuana started coming in right after the ballot initiative was passed in that state. But he said neurologists need to be deliberate in how they handle them.

“We need to understand which patients will be best served by the use of this treatment,” he said. “We also need to be more educated about the effects of marijuana, the potential complications and side effects associated with this. And there are other issues with respect to legality including driving while under the influence of marijuana.”

In general, he said, “you want to stick to standard of care, and that does not include marijuana,” he said.

In Washington State, where medical marijuana became legal in 1998, neurologists have not embraced its use, despite increasingly frequent requests from patients for epilepsy and other conditions, said David Vossler, MD, FAAN, chair of the Medications Work Group for the American Epilepsy Society and clinical associate professor of neurology at the University of Washington.

The interest in marijuana treatment is distinctly one-sided, said Dr. Vossler, who is also secretary-treasurer for the Washington State Neurological Society.

“It's almost always the patient coming in and asking for it,” he said. “Epileptologists like me don't generally recommended marijuana for our seizure patients, because there are no rigorous scientific studies done yet to show that it both works and is safe.”

One US study in children with catastrophic epilepsies is just beginning, he said, referring to the trial of Epidiolex. But for other neurological conditions, some providers in Washington State do occasionally prescribe cannabinoids when other treatment options fail. For example, he said, some of the state's neurology society members have seen it used effectively for pain or for spasticity due to ALS or MS.

“Most of the neurologists I have spoken with in Washington State are pretty reluctant to write [certifications] for it. We're concerned not only about the lack of scientific evidence for its effectiveness, but also about long-term side effects, quality control, where it comes from, what's really in the stuff the patients obtain, and just patient safety. Also, what is the prescriber's liability if an adverse effect occurs when patients are getting a federally-illegal substance from an unregulated dispensary?”

NEED FOR PROFESSIONAL EDUCATION

Despite the growing interest across the country, formal educational programming for neurologists has been slow in coming, but some sessions are now being organized. At the Massachusetts Neurologic Association, one of the three sessions at the association's spring meeting will be devoted to an overview of opioids and medical marijuana, Dr. Garcia said. Brian McGeeney, MD, MPH, an assistant professor of neurology at Boston University, will be giving the talk.

“The more information we have, the better we will be equipped to deal with questions from patients who come with a legitimate concern about their neurological problems,” Dr. Garcia said.

In Colorado, a conference is also being organized, Dr. London said.

“It's a bit under the radar from the physicians' point of view on how to handle all this,” he said. “This has been a real grassroots process, so it really had no large executive kind of body support and there has not been a mechanism that I'm aware of for training physicians or real authoritative educational opportunities.”

In Washington State, no events for education on medical marijuana are planned, Dr. Vossler said. The Washington State Neurological Society discussed holding a session at its next annual meeting, but opted against it.

“It seemed like there were a lot of other pressing needs,” he said.

Most neurologists agree that more rigorous research should be done.

Dr. Pearl in Massachusetts said he would especially support more research on cannabidiol for Dravet syndrome.

“We would strongly prefer to do this as part of a study and not just willy-nilly prescribing it,” said Dr. Pearl in Massachusetts. “We really don't have the scientific evidence for efficacy or safety. Basically there is enough anecdotal support for us to consider it and study it, but not to make any other conclusions.”

Dr. Vossler in Washington State said more rigorous work is needed, but that any results should be viewed with caution. He said he and the state's neurological society members support the position statement of the American Epilepsy Society, which says, in part, that research is “desperately needed” and that marijuana's status as a Schedule 1 substance be reviewed.

“The problem is, there's a lot of placebo effect, and a lot of willingness to believe that, ‘Hey, what I'm dong is helping me.’ And that kind of bias can really skew results…. At least for epilepsy patients, now that we have about 25 antiepileptic drugs, plus proven devices, diets, and surgery, it's certainly not one of the first six or eight therapies we're going to advise for our patients.”